Eco-friendly Synthesis of Some New Benzylidene-iminothiazolyl-pyrazol-3-ol Derivatives via One-Pot Multicomponent Reaction and Evaluation of Antioxidant Activities

In present work, one-pot multicomponent reaction (MCR) route for the synthesis of benzylideneiminothiazolyl- pyrazol-3-ol derivatives (5a-p) by reacting ethyl cyanoacetate (1), substituted benzaldehyde (2a-c), thiosemicarbazide (3) and substituted phenacyl bromide (4a-g). This reaction proceeds by using bleaching earth clay (BEC) (pH 12.5) in PEG-400 as a green reaction media. All the synthesized compounds were characterized by IR, 1H NMR, 13C NMR and mass spectral data. The pharmacological investigation of the synthesized compounds suggest that most of them showed good antioxidant activity.

Synthesis, Docking and Antimicrobial Activity of Some New Coumarin Incorporated Thiazole Derivatives

Synthesis and screening of a series of new coumarin derivatives coupled with thiazole are performed for their antimicrobial properties. A series of new thiazolyl coumarin derivatives were synthesized upon refluxing 3-bromoaceytl coumarin, substituted benzaldehyde and thiosemicarbazide in the presence of glacial acetic acid. Substituted 3-acetyl coumarin undergoes bromination in the presence of bromine and chloroform to form 3-Bromoaceytl coumarin. The thiazolyl coumarin derivatives were characterized based on IR, 1H NMR, and Mass spectral data. The docking studies have been carried out against the enzyme DNA gyrase (1KZN). Compound SCT 2 showed the highest docking score -5.662 compared to other compounds. The final synthesized compounds were screened for their antibacterial activity by tube dilution method. Compound SCT 1 and SCT 2 showed significant antibacterial activity with minimum inhibitory concentration of 12.5µg/ml and 6.25µg/ml, respectively, compared to standard Cephalosporin. The MIC results suggest that compounds SCT 1 and SCT 2 showed promising antibacterial activity. So these compounds are interesting lead molecules for further synthesis as antimicrobial agents.

Theophylline Derivatives' In-vivo Analgesic and Anti-Inflammatory Activities

The reaction of theophylline and chloro-acetyl chloride produced an exceptional series of substituted theophylline derivatives (3A-3D), followed by ammonium thiocyanate and substituted aromatic aldehyde, and these synthesized derivatives were screened to study their analgesic and anti-inflammatory activities. UV, IR, H-1 NMR, mass spectral data, and CHN activities were used to describe the compounds, which were shown to be considerably efficacious at 100 mg/kg p.o., as well as experimental results that were statistically significant at the p <0.01 and p <0.05 levels.

Phenylisoxazole-3/5-Carbaldehyde Isonicotinylhydrazone Derivatives: Synthesis, Characterization, and Antitubercular Activity

Eight new phenylisoxazole isoniazid derivatives, 3-(2′-fluorophenyl)isoxazole-5-carbaldehyde isonicotinylhydrazone (1), 3-(2′-methoxyphenyl)isoxazole-5-carbaldehyde isonicotinylhydrazone (2), 3-(2′-chlorophenyl)isoxazole-5-carbaldehyde isonicotinylhydrazone (3), 3-(3′-clorophenyl)isoxazole-5-carbaldehyde isonicotinylhydrazone (4), 3-(4′-bromophenyl)isoxazole-5-carbaldehyde isonicotinylhydrazone (5), 5-(4′-methoxiphenyl)isoxazole-3-carbaldehyde isonicotinylhydrazone (6), 5-(4′-methylphenyl)isoxazole-3-carbaldehyde isonicotinylhydrazone (7), and 5-(4′-clorophenyl)isoxazole-3-carbaldehyde isonicotinylhydrazone (8), have been synthesized and characterized by FT-IR, 1H-NMR, 13C-NMR, and mass spectral data. The 2D NMR (1H-1H NOESY) analysis of 1 and 2 confirmed that these compounds in acetone-d6 are in the trans(E) isomeric form. This evidence is supported by computational calculations which were performed for compounds 1–8, using DFT/B3LYP level with the 6-311++G(d,p) basis set. The in vitro antituberculous activity of all the synthesized compounds was determined against the Mycobacterium tuberculosis standard strains: sensitive H37Rv (ATCC-27294) and resistant TB DM97. All the compounds exhibited moderate bioactivity (MIC = 0.34–0.41 μM) with respect to the isoniazid drug (MIC = 0.91 μM) against the H37Rv sensitive strain. Compounds 6 (X = 4′-OCH3) and 7 (X = 4′-CH3) with MIC values of 12.41 and 13.06 μM, respectively, were about two times more cytotoxic, compared with isoniazid, against the resistant strain TB DM97.

SYNTHESIS OF 1-BENZOYL-3-PHENYL-1H-PYRAZOLE-4-CARBALDEHYDE AND EVALUATION OF THEIR ANTIOXIDANT AND ANTI-INFLAMMATORY ACTIVITY

Objective: The main objective of this study is to synthesize a series of 1-Benzoyl-3-phenyl-1H-pyrazole-4-carbaldehyde (4a-e) derivatives and evaluation of the synthesized compounds for their antioxidant and anti-inflammatory activity. Methods: A series of substituted acetophenones are condensed with hydrazides to the corresponding hydrazones which are subsequently cyclized by using vilsmier-Haack reaction to give final series of 1-Benzoyl-3-phenyl-1H-pyrazole-4-carbaldehyde (4a-e) derivatives respectively. All newly synthesized compounds were characterized on the basis of infrared, proton nuclear magnetic resonance and mass spectral data and screened for their antioxidant and anti-inflammatory activities. Results: In view of the significant biological activity profile of Pyrazole, the synthesized compounds (4a-e) were evaluated for their antioxidant potency by DPPH, Nitric oxide, Hydroxyl radical scavenging, and Hydrogen Peroxide method. Compounds 4c and 4e showed potent antioxidant activity then standard. Synthesized compounds were also screened for anti-inflammatory activity. Among all the molecules 4c, 4e, and 4d showed significant activity as compared to standard drug diclofenac sodium. Conclusion: in this study, we synthesized 1-Benzoyl-3-phenyl-1H-pyrazole-4-carbaldehyde (4a-e) derivatives. Further, these derivatives showed significant antioxidant and anti-inflammatory activity. Among them, two molecules 4c and 4e have shown near action to the standard.

In-silico Studies, Synthesis, and Antibacterial Evaluation of Thiophene Linked Isoxazole Derivatives

In this work a series of thiophene linked isoxazole derivatives (LK1-LK8) was synthesized by cyclization of different substituted thienyl chalcones (PL1-PL8). The structures of the synthesized compounds were characterized by IR, 1H NMR and mass spectral data. These derivatives were evaluated for antibacterial activities. Compounds LK7 showed excellent antibacterial activities amongst the synthesized compounds with MIC value 6.75 µg/ml. Molecular docking of these linked isoxazole derivatives (LK1-LK8) was also performed with crystal structure of staph gyrase B 24kDa (PDB code: 5 4URM). All the isoxazole derivatives (LK1-LK8) were docked into same groove of the binding site of native co-crystallized (1R,4aS,5S,6S,8aR)-5-{[(5S)-1-(3-O-acetyl-4-O-carbamoyl-6-deoxy-2-O-methyl-alpha-L-talopyra nosy l)-4 hydroxy 2-oxo-5-(propan-2-yl)-2,5-dihydro-1H-pyrrol-3-yl]carbonyl}-6-methyl-4 1, 2, 3, 4 methylid-ene,4a,5,6,8a-octahydronaphthalen-1-yl2,6-dideoxy-3-C-[(1S)-1-{[(3,4-dichloro-5-methyl-1 H-pyrrol-2-yl) carbonyl]amino}ethyl]-beta-D-ribo-hexopyranoside) ligand for activity explanation and exhibited good ligand interaction and binding affinity were of range -2.04 to -4.34 kcal/mol.

Investigation of Chemical Profiles of Different Parts of Morus alba Using a Combination of Molecular Networking Methods with Mass Spectral Data from Two Ionization Modes of LC/MS

Plants produce numerous secondary metabolites with diverse physicochemical properties. Because different parts of a single plant produce various components, several spectroscopic methods are necessary to inspect their chemical profiles. Mass spectral data are recognized as one of the most useful tools for analyzing components with a wide range of polarities. However, interpreting mass spectral data generated from positive and negative ionization modes is a challenging task because of the diverse chemical profiles of secondary metabolites. Herein, we combine and analyze mass spectral data generated in two ionization modes to detect as many metabolites as possible using the molecular networking approach. We selected different parts of a single plant, Morus alba (Moraceae), which are used in the functional food and medicinal herb industries. The mass spectral data generated from two ionization modes were combined and analyzed using various molecular networking workflows. We confirmed that our approach could be applied to simultaneously analyze the different types of secondary metabolites with different physicochemical properties.

Determination of phytocomponents and validation of squalene in ethanolic extract of Clerodendrum serratum Linn roots—using gas chromatography-mass spectroscopy and GC-FID technique

Background Clerodendrum serratum Linn commonly known as Bharangi in India has wide applications in the Ayurveda and Siddha system of medicine which has been attributed to the treatment of various diseases like asthma, cough, fever, rheumatism, and cephalalgia ophthalmia. Squalene has nutritional, medicinal, and pharmaceutical health benefits, hence possess antioxidant and cytoprotective effects. Method The study presents the GC-MS analysis of phytoconstituents present in the Clerodendrum serratum roots and further estimation of one of the constituents, i.e., squalene which is ought to be present in the roots as per mass spectral data obtained. Squalene was determined from the ethanolic extract of C. serratum roots using GC-FID without derivatization. Results Four major constituents, i.e., squalene, methyl palmitate, hexadecenoic acid, and stigmasterol were detected by GC-MS. Squalene from the extract was eluted at 17.5min which was confirmed with the standard squalene peak eluted at the same retention time. The linearity range chosen was 5–30ug/mL, and the method was found to be pretty linear (R=0.995), accurate with satisfactory repeatability. Hence, the phytochemical compounds were detected by GC-MS and the squalene was determined and validated according to the ICH guidelines. Conclusion Thus, the green gas chromatographic method can be used for quantification and qualification of active constituents in the roots of ethanolic extract of C. serratum. In addition, the presence of metabolite squalene by the GC-FID method was developed for the extract which is simple, fast, and environmentally friendly.

N-(Benzo[d]thiazol-2-yl)-2-(2-fluoro-[1,1′-biphenyl]-4-yl)propanamide

N-(Benzo[d]thiazol-2-yl)-2-(2-fluoro-[1,1′-biphenyl]-4-yl)propanamide was prepared by a reaction between benzo[d]thiazol-2-amine and flurbiprofen in high yield. The newly obtained flurbiprofen derivative was fully analyzed and characterized via 1H, 13C, UV, IR, and mass spectral data.

(E)-2,6,10-Trimethyldodec-8-en-2-ol: An Undescribed Sesquiterpenoid from Copaiba Oil

The use of copaiba oil has been reported since the 16th century in Amazon traditional medicine, especially as an anti-inflammatory ingredient and for wound healing. The use of copaiba oil continues today, and it is sold in various parts of the world, including the United States. Copaiba oil contains mainly sesquiterpenes, bioactive compounds that are popular for their positive effect on human health. As part of our ongoing research endeavors to identify the chemical constituents of broadly consumed herbal supplements or their adulterants, copaiba oil was investigated. In this regard, copaiba oil was subjected to repeated silica gel column chromatography to purify the compounds. As a result, one new and seven known sesquiterpenes/sesquiterpenoids were isolated and identified from the copaiba oil. The new compound was elucidated as (E)-2,6,10-trimethyldodec-8-en-2-ol. Structure elucidation was achieved by 1D- and 2D NMR and GC/Q-ToF mass spectral data analyses. The isolated chemical constituents in this study could be used as chemical markers to evaluate the safety or quality of copaiba oil.